title: Increased regulatory T cells and impaired functions of circulating CD8 T lymphocytes is associated with viral persistence in Hepatitis B virus-positive newborns.
abstract: Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.
authors.affiliation: Institute of Liver and Biliary Sciences, New Delhi, India; Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shrivastava
authors.forename: N
authors.initials: N
authors.lastname: TrehanPati
authors.forename: S
authors.initials: S
authors.lastname: Patra
authors.forename: S
authors.initials: S
authors.lastname: Kottilil
authors.forename: C
authors.initials: C
authors.lastname: Pande
authors.forename: S S
authors.initials: SS
authors.lastname: Trivedi
authors.forename: S K
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006514:Hepatitis B Surface Antigens; D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma
keywords: CD8 T-cell dysfunction; HBV-positive newborns; Peripheral Blood Mononuclear cells; T-cell function; T-cell receptor; regulatory T cells